title: Therapeutic drug monitoring of telaprevir in chronic hepatitis C patients receiving telaprevir-based triple therapy is useful for predicting virological response.
abstract: OBJECTIVE
  This prospective, pharmacokinetic study was done to investigate the impact of telaprevir plasma trough concentration (Ctrough) in the early stage of treatment on the response to telaprevir-based triple therapy for chronic hepatitis C patients.
  
  
  METHODS
  Participants were 70 chronic hepatitis C patients infected with genotype 1. All patients received 12 week triple therapy that included telaprevir (2250 mg/day), pegylated interferon-α2b (pegylated-IFNα2b) (60-150 μg/week) and ribavirin (600-1000 mg/day) followed by a 12 week dual therapy that included pegylated-IFNα2b and ribavirin. Plasma telaprevir Ctrough was determined by a validated assay using HPLC at days 3, 7 and 14. The study was registered as a clinical trial on the University Hospital Medical Information Network (ID 000009656).
  
  
  RESULTS
  The rates of undetectable hepatitis C virus RNA at week 4 [rapid virological response (RVR)] and at 24 weeks after therapy [sustained virological response (SVR)] were 71.4% and 82.9%, respectively. Of the patients with RVR, 90% achieved SVR. The mean telaprevir Ctrough levels at days 3, 7 and 14 of SVR patients (2.748, 2.733 and 2.999 μg/mL, respectively) were significantly higher than those of non-SVR patients (1.616, 1.788 and 2.314 μg/mL, respectively) (all P < 0.05). Multiple logistic regression analysis of possible predictors of SVR extracted higher telaprevir Ctrough at day 3 (OR 1.012 by 0.001 μg/mL, P < 0.0001) and interleukin 28B (rs8099917) TT allele (OR 6.16 versus non-TT alleles, P < 0.0001).
  
  
  CONCLUSIONS
  Therapeutic drug monitoring of telaprevir in the early stage of treatment is useful in clinical practice for predicting the virological response of patients receiving telaprevir-based triple therapy.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Murata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Toyoda
authors.forename: Hachiro
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Kunimitsu
authors.initials: K
authors.lastname: Eiraku
authors.forename: Motohiro
authors.initials: M
authors.lastname: Shimizu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Harada
authors.forename: Fujiko
authors.initials: F
authors.lastname: Mitsumoto
authors.forename: Koji
authors.initials: K
authors.lastname: Takayama
authors.forename: Mosaburo
authors.initials: M
authors.lastname: Kainuma
authors.forename: Kyoko
authors.initials: K
authors.lastname: Okada
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects / Q000379:methods
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b
keywords: pegylated interferon-α; plasma trough concentrations; ribavirin